Endocrine Abstracts

Introduction: Pancreatic neuroendocrine tumors (PNETs) originate from neuroendocrine islet cells and can therefore secrete several neuropeptides. Multiple and secondary hormone secretion have been described in a minority of cases, mostly with advanced disease, and it has been hypothesized that this complex secretion pattern can serve as a marker for tumor behavior.

Case report: Male patient, 69 years old, diagnosed with a glucagonoma with pulmonary and hepatic metastasis, in 2009. He was sequentially treated with chemotherapy (gemcitabine and CAPTEM), octreotide, PRRT and everolimus, and lastly with sunitinib. He also had diabetes mellitus, likely secondary to the glucagonoma, well controlled with insulin therapy. The patient presented with recurrent symptomatic hypoglycemia that persisted despite insulin suspension. Bloodwork showed glucose 36 mg/dl, C peptide 6,95 (1.1-5.0) ng/ml and insulin 39,2 (2.6-24.9) uUI/ml and the diagnosis of insulinoma was assumed. He started therapy with diazoxide and lanreotide, for hypersecretion control, with a later switch to pasireotide for its hyperglycemic effects. The ⁶⁸Ga-DOTANOC PET/CT showed hepatic disease progression and he was submitted to 2 additional cycles of PRRNT. None of these measures led to normoglycemia so corticotherapy was introduced. Recurrent severe hypoglycemia with frequent visits to the emergency department led to the patient’s hospitalization in our center. Several measures were applied to try to rise his glycemic levels: glucagon perfusion, subcutaneous octreotide 3id, higher steroid doses, 30% glucose perfusion and everolimus (due to its hyperglycemic effect), with little benefit. Considering the hepatic disease progression, (radio) embolization was contemplated, but after discussion with interventional radiology and nuclear medicine, not deemed feasible due to porto-systemic shunt. During the hospital stay, the patient’s clinical picture progressively deteriorated, and he passed away shortly after the diagnosis of SARS-COV2 infection.

Conclusion: This case highlights the PNETs ability to change their secretion profile, usually described in the context of advanced and aggressive disease. Several therapeutic lines were used in this patient, with no significant effect, underlying the need for new alternatives for aggressive and refractory insulinomas. Targeted alpha-particle therapies like ²²⁵Ac-DOTATATE have been described with great results in this type of patients but, unfortunately, they are still not available in our country.